Hepatic mitochondrial malondialdehyde metabolism in rats with chronic iron overload.
Peroxidative decomposition of mitochondrial membrane phospholipids with subsequent mitochondrial dysfunction is a postulated mechanism of liver cell injury in parenchymal iron overload. Malondialdehyde is formed when polyunsaturated fatty acids of membrane phospholipids undergo peroxidative decomposition, and it is metabolized by aldehyde dehydrogenase. We studied mitochondrial metabolism of malondialdehyde in rats with chronic dietary iron overload. Hepatic malondialdehyde concentrations were significantly increased in iron-loaded livers, and mitochondrial respiratory control ratios using glutamate as a substrate were decreased by 47% largely owing to reductions in state 3 respiration. When exogenous malondialdehyde was added to mitochondrial fractions, there was significantly less metabolism of malondialdehyde in mitochondria of iron-loaded livers as compared with controls. In addition, there was a 28% decrease in mitochondrial aldehyde dehydrogenase in iron-loaded livers but no change in cytosolic aldehyde dehydrogenase. Increased hepatic malondialdehyde in chronic iron overload may result from a combination of increased production and decreased metabolism of malondialdehyde, both of which may be due to iron-induced mitochondrial lipid peroxidation.
Britton
R S
RS
Department of Medicine, Case Western Reserve University School of Medicine, Cleveland Metropolitan General Hospital, Ohio 44109.
O'Neill
R
R
Bacon
B R
BR
D000444:Aldehyde Dehydrogenase / Q000032:analysis; D000818:Animals; D007501:Iron / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D015227:Lipid Peroxidation; D008297:Male; D008314:Malonates / Q000378:metabolism*; D008315:Malondialdehyde / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D008314:Malonates; D008315:Malondialdehyde; D007501:Iron; D000444:Aldehyde Dehydrogenase